海洋性貧血

Buzzwords → Dx

Diagnostic Criteria

• CBC + smear: microcytic, hypochromic, target cells, normal/high RBC count, ↓MCV.
• Mentzer index (MCV/RBC) <13 suggests thalassemia trait; >13 suggests IDA (rough).
• Hb electrophoresis or HPLC:
  • β-thal trait: HbA₂ >3.5 %, sometimes ↑HbF.
  • β-thal major/intermedia: ↑↑HbF, variable HbA₂, low/absent HbA.
  • α-thal trait (silent or trait): electrophoresis often normal at adult age — need genetic testing.
  • HbH disease: HbH (β₄) detectable on electrophoresis.
  • Hb Bart's hydrops: Hb Bart's (γ₄) on neonatal screen.
• α-globin gene PCR / MLPA for confirmation (deletion analysis).
• Iron studies to rule out concurrent IDA.

Workup

• CBC + smear + retic + iron studies + ferritin.
• Hb electrophoresis or HPLC.
• α-globin gene analysis (PCR or MLPA) if α-thal suspected.
• Family history + ancestry.
• Genetic counseling for partners (couples planning children).
• Iron overload monitoring (ferritin, MRI T2* hepatic + cardiac) in transfusion-dependent.
• Endocrine workup in transfusion-dependent (TSH, glucose, calcium, gonadal hormones).

Treatment Algorithm

flowchart TD
  A[Microcytic anemia, normal RBC] --> B[Hb electrophoresis + α-globin testing]
  B --> C{Severity}
  C -- trait (silent / minor) --> D[No treatment<br>genetic counseling]
  C -- HbH disease<br>(α-thal 3-gene deletion) --> E[Folate + intermittent transfusion<br>splenectomy if hypersplenism<br>avoid iron supplements]
  C -- β-thal intermedia --> F[Folate + selective transfusion<br>luspatercept can reduce transfusion need<br>splenectomy / hydroxyurea (HbF inducer)]
  C -- β-thal major / Cooley --> G[Lifelong RBC transfusion<br>target Hb >9 g/dL<br>+ iron chelation MANDATORY]
  G --> H[Iron chelation:<br>deferoxamine SC overnight, deferasirox PO, deferiprone PO]
  G --> I{Curative options}
  I -- HLA-matched sibling --> J[Allo-HCT in childhood]
  I -- no donor + severe --> K[Gene therapy<br>Casgevy / Lyfgenia<br>FDA approved 2023]
  G --> L[Cardiac MRI T2* annually<br>endocrine + bone density monitoring]
  F --> M[Pregnancy: high-risk; transfusion + chelation modifications]
  G --> M

Pearls / Pitfalls

• Don't mistake thalassemia for IDA: thalassemia has normal-to-high RBC count + target cells + low Mentzer index. Iron studies normal-to-high. Don't give iron unless concurrent deficiency confirmed.
• Bart's hydrops fetalis (–/–) is incompatible with life — universal screening in high-prevalence populations + genetic counseling.
• HbH disease (–/–α) = moderately severe anemia; supportive + folate + intermittent transfusion. Avoid oxidative drugs (similar to G6PD).
• β-thal A₂ elevation (>3.5 %) is diagnostic for β-thal trait — HbA₂ may be artificially low in concurrent iron deficiency (re-test after iron repletion if uncertain).
• β-thal major transfusion target = pre-transfusion Hb 9–10.5 g/dL — too low → ineffective erythropoiesis worsens skeletal deformities; too high → iron overload accelerates.
• Iron chelation regimens:
  • Deferoxamine (DFO): SC infusion 8–10 h overnight, 5 d/wk; original gold standard.
  • Deferasirox: PO once daily; renal monitoring.
  • Deferiprone: PO TID; cardiac iron preference; agranulocytosis monitoring (CBC every 1–2 wk).
• Cardiac iron is the leading mortality cause in transfused β-thal. MRI T2 <20 ms* = significant cardiac loading.
• Luspatercept approved for transfusion-dependent β-thal — reduces transfusion burden by ~30 %; SC q3 wk (BELIEVE trial).
• Gene therapy (Casgevy = exa-cel CRISPR BCL11A; Lyfgenia = lovo-cel lentiviral) approved for transfusion-dependent β-thal; severe SCD eligible too.
• Allogeneic HCT in matched sibling is curative — best in young pts before iron damage accumulates.
• Endocrine complications in transfused β-thal: hypogonadism, hypothyroid, diabetes, hypoparathyroid, osteoporosis. Annual screening.
• Splenectomy in β-thal intermedia → risk of pulmonary HTN + thrombosis (esp. post-splenectomy thrombocytosis); careful selection.
• Hereditary persistence of fetal Hb (HPFH) is benign; high HbF on electrophoresis without anemia.
• Sickle-β-thal (HbS-β⁰ or HbS-β⁺) behaves like SCD — see SCD.

Cross-references

• IDA — DDx
• SCD — sickle-β-thal compound
• Other Hb variants
• Allo-HCT for severe β-thal
• Iron Chelation

相關題目

• Q-127 — Thalassemia trait vs IDA
• Q-128 — β-thal major — luspatercept
• Q-129 — HbE-β-thal severity
• Q-208 — Iron chelation indications
• Q-209 — Iron chelation — cardiac iron preference

Sources